Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 18, Issue 11, Pages -Publisher
MDPI AG
DOI: 10.3390/ijms18112394
Keywords
apoptosis; autophagy; steroid receptors; xenobiotic receptors; nervous system; estrogen receptors
Funding
- KNOW - Ministry of Science and Higher Education in Poland
- KNOW [MNiSW-DS-6002-4693-26/WA/12, E459-9740-DE16-84DC-0D41/CBED-3F5F-92FC-0480-D0B4]
- National Science Centre, Poland [2015/19/B/NZ7/02449]
- Institute of Pharmacology Polish Academy of Sciences, Krakow, Poland
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Apoptosis and autophagy are involved in neural development and in the response of the nervous system to a variety of insults. Apoptosis is responsible for cell elimination, whereas autophagy can eliminate the cells or keep them alive, even in conditions lacking trophic factors. Therefore, both processes may function synergistically or antagonistically. Steroid and xenobiotic receptors are regulators of apoptosis and autophagy; however, their actions in various pathologies are complex. In general, the estrogen (ER), progesterone (PR), and mineralocorticoid (MR) receptors mediate anti-apoptotic signalling, whereas the androgen (AR) and glucocorticoid (GR) receptors participate in pro-apoptotic pathways. ER-mediated neuroprotection is attributed to estrogen and selective ER modulators in apoptosis- and autophagy-related neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases, stroke, multiple sclerosis, and retinopathies. PR activation appeared particularly effective in treating traumatic brain and spinal cord injuries and ischemic stroke. Except for in the retina, activated GR is engaged in neuronal cell death, whereas MR signalling appeared to be associated with neuroprotection. In addition to steroid receptors, the aryl hydrocarbon receptor (AHR) mediates the induction and propagation of apoptosis, whereas the peroxisome proliferator-activated receptors (PPARs) inhibit this programmed cell death. Most of the retinoid X receptor-related xenobiotic receptors stimulate apoptotic processes that accompany neural pathologies. Among the possible therapeutic strategies based on targeting apoptosis via steroid and xenobiotic receptors, the most promising are the selective modulators of the ER, AR, AHR, PPAR gamma agonists, flavonoids, and miRNAs. The prospective therapies to overcome neuronal cell death by targeting autophagy via steroid and xenobiotic receptors are much less recognized.
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